Isotopic studies of the biosynthesis of the cerebroside fatty acids in rats

Abstract

SUMMARY Groups of weanling rats were given a single injection of labeled acetate and were sacrificed at intervals up to 56 days. The saturated acids of brain cerebrosides and brain were isolated by gas-liquid chromatography, counted, and chemically degraded to measure the distribution of activity. The total activity in the cerebroside acids, except 18:0, increased with time over a period of 14 days or more, then slowly decreased. The latter period of decreasing activity shows that these acids undergo metabolic conversion. Degradation of the acids showed the carboxyl group had a maximal relative activity at around 4 hr, which declined with time toward values close to or below that expected for de novo synthesis from acetate. From these observations, it was concluded that the cerebroside acids are made by a chainlengthening process from one or more shorter fatty acids. The relative activity in the carboxyl of 23h:O decreased very rapidly with time and the activity in its a-carbon reached a high value; from this it is concluded that this acid is made by two enzyme systems, one being a 1-carbon degradation of a CZ4 acid. The later samples of cerebroside 18:O showed uniform distribution of activity, suggesting that it is made directly from acetate. The 16:O of total brain showed the same effect, while the 18:O of whole brain resembled the cerebroside longer acids. The specific activity data suggested that the hydroxy and normal acids are made from a common precursor.